Usage
- Mianserin is prescribed for the treatment of major depressive disorder. It may also be used off-label for insomnia at lower doses.
- Pharmacological classification: Tetracyclic antidepressant (TeCA).
- Mechanism of action: Mianserin enhances noradrenergic and serotonergic neurotransmission by blocking presynaptic α2-adrenergic autoreceptors and α2-adrenergic heteroreceptors located on serotonergic neurons. It also acts as an antagonist at 5-HT2A, 5-HT2C, 5-HT3, and H1 receptors. Mianserin’s antidepressant effect is primarily thought to be related to its noradrenergic effects and 5-HT2 antagonism.
Alternate Names
- Mianserin hydrochloride
- Brand Names: Tolvon, Lumin, Norval
How It Works
- Pharmacodynamics: Mianserin increases noradrenergic and serotonergic neurotransmission by blocking presynaptic α2-adrenergic autoreceptors and heteroreceptors. It also antagonizes 5-HT2A, 5-HT2C, 5-HT3, and H1 receptors. Its therapeutic effect in depression is believed to be mediated through the noradrenergic effects and 5-HT2 antagonism.
- Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6. Desmethylmianserin is the major active metabolite.
- Elimination: Primarily eliminated through hepatic metabolism and subsequent renal excretion. The half-life is prolonged in the elderly.
- Mode of action: Antagonism of presynaptic α2-adrenergic autoreceptors on noradrenergic neurons increases noradrenaline release. Antagonism of α2-adrenergic heteroreceptors on serotonergic neurons increases serotonin release. Antagonism of 5-HT2 receptors is thought to contribute to its antidepressant and anxiolytic effects. 5-HT3 and H1 receptor antagonism likely contribute to side effects such as sedation and weight gain.
- Receptor binding: α2-adrenergic autoreceptor and heteroreceptor antagonist, 5-HT2A, 5-HT2C, 5-HT3, and H1 receptor antagonist.
- Elimination pathways: Hepatic metabolism (CYP2D6) and renal excretion.
Dosage
Standard Dosage
Adults:
- Initial: 30-40 mg daily, taken as a single dose at bedtime or in divided doses.
- Maintenance: 30-90 mg daily. May increase up to a maximum of 120-200 mg daily in divided doses.
- The bedtime dose may improve sleep.
Children:
- Mianserin is not recommended for use in children and adolescents under 18 years of age due to increased risk of suicidal ideation and behavior.
Special Cases:
- Elderly Patients: Initial dose not to exceed 30 mg daily, titrated gradually as needed. A lower maintenance dose may be sufficient. A single bedtime dose is preferred.
- Patients with Renal Impairment: Caution is advised; dosage adjustments may be necessary depending on the degree of impairment. Monitor renal function.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution and dose adjustments are necessary in mild to moderate hepatic dysfunction.
- Patients with Comorbid Conditions: Caution in patients with epilepsy, diabetes, cardiovascular disease, glaucoma, prostatic hypertrophy, and history of suicidal ideation.
Clinical Use Cases
- Mianserin is not typically indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is for the treatment of major depressive disorder.
Dosage Adjustments:
- Adjust dosage based on patient response and tolerability.
- Reduce dosage in renal or hepatic impairment.
- Consider drug interactions and comorbidities when adjusting the dosage.
Side Effects
Common Side Effects:
- Drowsiness, sedation
- Dry mouth
- Constipation
- Weight gain
- Dizziness, vertigo
- Tremor
Rare but Serious Side Effects:
- Suicidal ideation and behavior
- Seizures
- Agranulocytosis, leukopenia, thrombocytopenia
- Jaundice, hepatitis
- Hypomania, mania
- Cardiac arrhythmias, including QT prolongation
- Orthostatic hypotension
Long-Term Effects:
- Potential for withdrawal symptoms upon discontinuation.
- Weight gain
Adverse Drug Reactions (ADR):
- Agranulocytosis, leukopenia, thrombocytopenia
- Jaundice, hepatitis
- Seizures
- Suicidal ideation and behavior
- Cardiac arrhythmias, including QT prolongation
Contraindications
- Hypersensitivity to mianserin
- Mania
- Severe hepatic impairment
- Concomitant use of MAOIs
Drug Interactions
- MAOIs: Contraindicated due to risk of serotonin syndrome.
- CNS depressants: Increased sedation (e.g., alcohol, benzodiazepines, antipsychotics).
- Antiepileptics: May lower seizure threshold; reduced efficacy of mianserin with enzyme-inducing antiepileptics (e.g., carbamazepine, phenytoin, phenobarbital).
- Antihypertensives: May enhance hypotensive effects (e.g., diazoxide, hydralazine, nitroprusside).
- CYP2D6 inhibitors: May increase mianserin levels (e.g., fluoxetine, paroxetine).
- CYP2D6 inducers: May decrease mianserin levels (e.g., rifampin, carbamazepine).
Pregnancy and Breastfeeding
- Pregnancy: Limited human data. Use only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: Mianserin is present in breast milk. Use with caution and monitor the infant for adverse effects.
Drug Profile Summary
- Mechanism of Action: Tetracyclic antidepressant that enhances noradrenergic and serotonergic transmission, and antagonizes 5-HT2, 5-HT3, and H1 receptors.
- Side Effects: Drowsiness, dry mouth, constipation, weight gain, dizziness, tremor. Rare but serious: suicidal ideation, seizures, blood dyscrasias, hepatic dysfunction, cardiac arrhythmias.
- Contraindications: Hypersensitivity, mania, severe hepatic impairment, concomitant use of MAOIs.
- Drug Interactions: MAOIs, CNS depressants, antiepileptics, antihypertensives, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Limited data; use with caution if potential benefit outweighs risk.
- Dosage: Adults: 30-90 mg/day; elderly: initial dose ≤ 30 mg/day.
- Monitoring Parameters: Monitor for mood changes, suicidal ideation, blood counts, liver function tests, and ECG in patients at risk for QT prolongation.
Popular Combinations
- Mianserin is not typically used in combination with other antidepressants.
Precautions
- General Precautions: Monitor for worsening of depression, suicidal ideation, and unusual changes in behavior.
- Specific Populations:
- Pregnant Women: Use with caution if the potential benefit outweighs the risk.
- Breastfeeding Mothers: Monitor infant for adverse effects.
- Children & Elderly: Not recommended for use in children under 18. Elderly patients require lower initial and maintenance doses.
- Lifestyle Considerations: Avoid alcohol, as it may potentiate sedative effects. Caution when operating machinery or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mianserin?
A: Adults: Initial dose 30-40 mg/day, increasing to 30-90 mg/day as needed. Elderly: Initial dose not to exceed 30 mg/day. Not recommended for children under 18.
Q2: What are the common side effects of Mianserin?
A: Drowsiness, dry mouth, constipation, weight gain, dizziness, and tremor are common side effects.
Q3: What are the serious side effects of Mianserin?
A: Suicidal ideation, seizures, blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia), hepatic dysfunction, and cardiac arrhythmias, including QT prolongation, are rare but serious side effects.
Q4: What are the contraindications for Mianserin?
A: Hypersensitivity to mianserin, mania, severe hepatic impairment, and concomitant use of MAOIs are contraindications.
Q5: Can Mianserin be used during pregnancy?
A: Limited human data is available. Use only if the potential benefit outweighs the potential risk to the fetus.
Q6: Can Mianserin be used during breastfeeding?
A: Mianserin is excreted in breast milk. Use with caution and monitor the infant for adverse effects. Discuss the risks and benefits with the patient.
Q7: Does Mianserin interact with other medications?
A: Yes, Mianserin interacts with MAOIs, CNS depressants, antiepileptics, antihypertensives, and drugs that inhibit or induce CYP2D6.
Q8: What is the mechanism of action of Mianserin?
A: Mianserin is a tetracyclic antidepressant that enhances noradrenergic and serotonergic transmission. It also blocks α2-adrenergic receptors (both autoreceptors and heteroreceptors) and antagonizes 5-HT2, 5-HT3, and H1 receptors.
Q9: How long does it take for Mianserin to work?
A: It may take several weeks for the full antidepressant effects of Mianserin to be observed.
Q10: What should I do if a patient misses a dose of Mianserin?
A: If it is close to the next scheduled dose, skip the missed dose and continue with the regular dosing schedule. Do not double the dose.
